Safety and effectiveness of monovalent COVID-19 mRNA vaccination and risk factors for hospitalisation caused by the omicron variant in 0.8 million adolescents: A nationwide cohort study in Sweden

Background Real-world evidence on the safety and effectiveness of Coronavirus Disease 2019 (COVID-19) vaccination against severe disease caused by the omicron variant among adolescents is sparse. In addition, evidence on risk factors for severe COVID-19 disease, and whether vaccination is similarly effective in such risk groups, is unclear. The aim of the present study was therefore to examine the safety and effectiveness of monovalent COVID-19 mRNA vaccination against COVID-19 hospitalisation, and risk factors for COVID-19 hospitalisation in adolescents. Methods and findings A cohort study was conducted using Swedish nationwide registers. The safety analysis included all individuals in Sweden born between 2003 and 2009 (aged 11.3 to 19.2 years) given at least 1 dose of monovalent mRNA vaccine (N = 645,355), and never vaccinated controls (N = 186,918). The outcomes included all-cause hospitalisation and 30 selected diagnoses until 5 June 2022. The vaccine effectiveness (VE) against COVID-19 hospitalisation, and risk factors for hospitalisation, were evaluated in adolescents given 2 doses of monovalent mRNA vaccine (N = 501,945), as compared to never vaccinated controls (N = 157,979), for up to 5 months follow-up during an omicron predominant period (1 January 2022 to 5 June 2022). Analyses were adjusted for age, sex, baseline date, and whether the individual was born in Sweden. The safety analysis showed that vaccination was associated with 16% lower (95% confidence interval (CI) [12, 19], p < 0.001) risk of all-cause hospitalisation, and with marginal differences between the groups regarding the 30 selected diagnoses. In the VE analysis, there were 21 cases (0.004%) of COVID-19 hospitalisation among 2-dose recipients and 26 cases (0.016%) among controls, resulting in a VE of 76% (95% CI [57, 87], p < 0.001). Predominant risk factors for COVID-19 hospitalisation included previous infections (bacterial infection, tonsillitis, and pneumonia) (odds ratio [OR]: 14.3, 95% CI [7.7, 26.6], p < 0.001), and cerebral palsy/development disorders (OR: 12.7, 95% CI [6.8, 23.8], p < 0.001), with similar estimates of VE in these subgroups as in the total cohort. The number needed to vaccinate with 2 doses to prevent 1 case of COVID-19 hospitalisation was 8,147 in the total cohort and 1,007 in those with previous infections or developmental disorders. None of the individuals hospitalised due to COVID-19 died within 30 days. Limitations of this study include the observational design and the possibility of unmeasured confounding. Conclusions In this nationwide study of Swedish adolescents, monovalent COVID-19 mRNA vaccination was not associated with an increased risk of any serious adverse events resulting in hospitalisation. Vaccination with 2 doses was associated with a lower risk of COVID-19 hospitalisation during an omicron predominant period, also among those with certain predisposing conditions who should be prioritised for vaccination. However, COVID-19 hospitalisation in the general population of adolescents was extremely rare, and additional doses in this population may not be warranted at this stage. Author summary Why was this study done? Evidence before this study. There is limited evidence on the effectiveness of Coronavirus Disease 2019 (COVID-19) vaccination against severe outcomes during the omicron era among adolescents. In addition, there is lack of data on whether certain groups of adolescents are at greater risk of severe COVID-19 and should be prioritised in vaccination programs, and whether vaccination is equally effective in such risk groups. Regarding safety, some studies have indicated a link between COVID-19 mRNA vaccination and increased risk of myocarditis and pericarditis in young men. What did the researchers do and find? Using Swedish nationwide health registers, a nationwide cohort of adolescents were followed for up to 5 months during the omicron era to evaluate the safety and effectiveness of monovalent COVID-19 mRNA vaccination against COVID-19 hospitalisation, and risk factors for COVID-19 hospitalisation. Adolescents vaccinated with at least 1 dose of a monovalent COVID-19 mRNA vaccine did not have a higher risk of hospitalisation for any diagnosis, as compared to unvaccinated adolescents. In contrast, individuals vaccinated with 2 doses of vaccine had 76% lower risk of being hospitalised due to COVID-19, although only about 7 individuals in 100,000 were hospitalised due to COVID-19 during follow-up. There were specific risk factors for COVID-19 hospitalisation, including previous infections and different development disorders, which increased the risk of COVID-19 hospitalisation more than 10-fold. Vaccine effectiveness among these individuals was similar as in the rest of the cohort. What do these findings mean? Although monovalent COVID-19 mRNA vaccination appears safe and associated with reduced risk of COVID-19 hospitalisation, the risk of severe COVID-19 seems to be extremely low in the general population of adolescents. Administration of additional vaccine doses to the general population of adolescents may not be warranted at this stage of the pandemic. In contrast, individuals with a high risk for severe COVID-19 should be prioritised for vaccination.

Automated summary

This study examined the safety and effectiveness of COVID-19 vaccination in adolescents and identified risk factors for COVID-19 hospitalisation. The results showed that COVID-19 vaccination did not increase the risk of hospitalisation in adolescents, and receiving 2 doses of the vaccine was associated with a lower risk of COVID-19 hospitalisation, particularly in high-risk groups. However, the risk of severe COVID-19 in the general adolescent population was extremely low, indicating that additional vaccine doses may not be necessary at this stage of the pandemic.